Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In conscious deoxycorticosterone acetate (DOCA) salt-hypertensive dogs, the angiotensin-converting enzyme (ACE) inhibitors captopril and imidaprilat significantly decreased mean arterial pressure (MAP) and significantly increased urine flow rate, effective renal plasma flow (ERPF), glomerular filtration rate, and urinary sodium excretion. However, the angiotensin type 1 (AT1) receptor antagonist losartan caused a significant increase only in urinary sodium excretion without significant changes in MAP, urine flow rate, ERPF, and glomerular filtration rate. Simultaneous infusion of a bradykinin receptor antagonist inhibited the ACE inhibitor-induced reduction in MAP and increase in ERPF. DOCA salt treatment markedly suppressed plasma angiotensin II (ANG II) concentration (P < 0.001), although it decreased renal ANG II content only slightly (P < 0.05). Comparison of the expression of renal AT1 receptor mRNA in control kidneys with that in DOCA salt-hypertensive kidneys revealed no significant change. These results suggest that, in low-renin hypertension, inhibition of the relatively maintained ANG II production in the kidney participates in the natriuretic action of ACE inhibitors. However, hypotensive and other renal effects are mainly due to the action of bradykinin.
 ...
PMID:Role of kinin and renal ANG II blockade in acute effects of ACE inhibitors in low-renin hypertension. 912 24

Left ventricular hypertrophy (LVH) is considered to be an independent risk factor giving rise to ischemia, arrhythmia, and left ventricular dysfunction. In this article, we summarize recent studies performed in our laboratory to investigate (1) the contribution of the renin-angiotensin system to the cardiac remodeling process, which is triggered by myocardial infarction (MI) or hypertension-induced cardiac hypertrophy; (2) the effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin AT1 receptor antagonism on cardiac parameters, such as myocardial infarct size, cardiac hypertrophy, heart function, and myocardial metabolism; (3) the mechanism of an ACE inhibitor-induced increase in cardiac capillary density in spontaneously hypertensive rats (SHR) and stroke prone SHR (SHR-SP). We observed that AT1 receptor gene expression in rat vascular smooth muscle cells (but not in rat coronary endothelial cells) was markedly enhanced after an ischemic insult in vitro. In a rat model in which MI was induced by coronary artery ligation, the AT1 receptor mRNA levels were transiently increased after MI and reached a peak level 24 hours post-MI. The AT2 receptor gene expression increased in a pattern similar to that of the AT1 receptor. ACE expression at the protein level in the repairing scar, which was demonstrated by monoclonal antibody staining, started to increase 2 weeks after MI and reached a peak level 3 weeks post-MI. Furthermore, long-term treatment with an ACE inhibitor limited infarct size, prevented cardiac hypertrophy, and improved heart function in the rat MI model. In SHR-SP, long-term treatment with either an ACE inhibitor or an AT1 receptor antagonist improved cardiac function and metabolism. Cardiac metabolism was even improved after low-dose ACE inhibitor treatment, which did not prevent hypertension and cardiac hypertrophy. In both SHR and SHR-SP, we found that the ACE inhibitor ramipril significantly increased capillary length density independently of its antihypertensive and antihypertrophic actions. Most of the cardiac effects of the ACE inhibitor could be abolished by a bradykinin B2 receptor antagonist. Thus, these cardiac effects of ACE inhibitors can be ascribed, at least under our experimental conditions, to ACE inhibitor-induced bradykinin potentiation.
 ...
PMID:Effects of angiotensin-converting enzyme inhibition and angiotensin II AT1 receptor antagonism on cardiac parameters in left ventricular hypertrophy. 929 63

Avid Na+ retention is a hallmark of liver cirrhosis. The aim of this study was to investigate whether and how bradykinin is involved in Na+ retention in rats with CCl4-induced liver cirrhosis. To this end the bradykinin B2 receptor antagonist Icatibant (HOE 140) was used. On one hand, bradykinin has a renal natriuretic action. On the other hand, bradykinin is a potent mediator of both vasodilation and microvascular leakage. Both vascular mechanisms, which are reported for cirrhosis, could cause vascular underfilling and Na+ retention by activating the renin-angiotensin-aldosterone system. Icatibant normalised Na+ retention and reduced the hyperactivity of the renin-angiotensin-aldosterone system, suggesting a bradykinin-induced vascular disturbance. Icatibant had no significant effect on the mild hypotension which developed with CCl4 treatment. However, there was indirect evidence for enhanced microvascular leakage that was strongly inhibited by Icatibant. Our experimental results demonstrate that bradykinin is a key mediator of Na+ retention in liver cirrhosis and suggest that a bradykinin-induced increase in microvascular leakage is mainly responsible.
 ...
PMID:The bradykinin B2 receptor antagonist Icatibant (HOE 140) corrects avid Na+ retention in rats with CCl4-induced liver cirrhosis: possible role of enhanced microvascular leakage. 938 80

Neuropeptide Y (NPY) is a co-transmitter of the sympathetic nervous system including the renal nerves. The kidney expresses NPY receptors, which can also be activated by peptide YY (PYY), a circulating hormone released from gastrointestinal cells. Five subtypes of NPY receptors have been cloned, among which Y1, Y2 and Y5 appear to be involved in the regulation of renal function. NPY produces potent renal vasoconstriction in vitro in isolated interlobar arteries and in the isolated perfused kidney and in vivo upon intrarenal or systemic administration via a Y1 receptor. Nevertheless glomerular filtration rate is altered only little if at all by NPY, indicating a greater effect on the vas efferens than the vas afferens. NPY can inhibit renin release via Y1-like receptors. NPY can stimulate Na+/K+ adenosine triphosphatase (Na+/K+-ATPase) in proximal tubules via Y2 receptors and can antagonize the effects of vasopressin on isolated collecting ducts. It can also act prejunctionally to inhibit noradrenaline release via Y2 receptors. Despite the profound reductions of renal blood flow, systemic NPY infusion can cause diuresis and natriuresis; this is largely independent of pressure natriuresis mechanisms and is possibly mediated by an extrarenal Y5 receptor. Studies with the converting enzyme inhibitor ramiprilat and the bradykinin receptor antagonist icatibant indicate that bradykinin mediates, at least partly, diuretic NPY effects. NPY antagonists enhance basal renal blood flow but do not alter basal diuresis or natriuresis indicating that renovascular, but not tubular, NPY receptors may be tonically activated by endogenous NPY.
 ...
PMID:Renal effects of neuropeptide Y. 944 90

The effects of N-type calcium channel inhibition with omega-conotoxin GVIA (omega-CTX) on cardiovascular parameters and vagally mediated autonomic reflexes and the role of the renin-angiotensin system were assessed in conscious rabbits. Omega-CTX (10 microg/kg, i.v.) resulted in hypotension, tachycardia, and attenuation of the sympathetic and vagal components of the baroreceptor-heart rate reflex (baroreflex). In the control group (no pretreatment), the peak decrease in mean arterial pressure (MAP) of 13 +/- 3 mm Hg from 72 +/- 2 mm Hg occurred after 33 +/- 3 min, with a corresponding tachycardia of 80 +/- 20 beats/min (n = 6). The tachycardia was due to vagal withdrawal, as a similar increase in heart rate (84 +/- 8 beats/min) after omega-CTX was observed after pretreatment with the beta-adrenoceptor antagonist, propranolol (n = 6). Angiotensin-converting enzyme (ACE) inhibition with enalaprilat revealed a larger, more rapid decrease in MAP in response to omega-CTX (-19 +/- 4 mm Hg from 65 +/- 1 mm Hg after 18 +/- 2 min; n = 6) compared with the control group. Similar larger decreases in MAP were also observed in the presence of the AT1-receptor antagonist, losartan, or the bradykinin B2 receptor antagonist, HOE-140 (n = 5-6). Pretreatment with enalaprilat, losartan, or HOE-140 caused a 50% decrease in the reflex tachycardia after omega-CTX compared with that observed in the control group, and omega-CTX caused a greater attenuation of the vagal component of the baroreflex and a decrease in the bradycardia evoked by the Bezold-Jarisch-like reflex. Also, there was a significant decrease in the bradycardia induced by the nasopharyngeal reflex after omega-CTX in the presence of ACE inhibition and HOE-140. Thus in the conscious rabbit, angiotensin II and bradykinin have a role in attenuating and slowing the hypotensive effect of N-type calcium channel inhibition. Vagolytic effects of omega-CTX on the baroreflex are augmented, and on other vagal reflexes are unmasked, via inhibition of the renin-angiotensin system. The complexity and mechanism of the interaction between N-type calcium channels and the renin-angiotensin system remain to be elucidated.
 ...
PMID:Endogenous angiotensin II and bradykinin delay and attenuate the hypotension after N-type calcium channel blockade in conscious rabbits. 986 1

Kinins have been shown to play an important role in the cardioprotective effect of ACE inhibitors (ACEi) during heart failure and ischemia-reperfusion. However, it is controversial as to whether kinins oppose the hypertensinogenic effect of deoxycorticosterone acetate plus salt (DOCA-salt) or aortic coarctation and whether they mediate both chronic antihypertensive and cardiac antihypertrophic effects of ACEi in hypertension. Using normal 129/SvEvTac mice and mice lacking the bradykinin B2 receptor gene (B2-KO), we investigated whether (1) the hypertensinogenic effect of DOCA-salt or aortic coarctation is enhanced in B2-KO mice and (2) the chronic antihypertensive and antihypertrophic effects of an ACEi (ramipril, 4 mg. kg-1. d-1) are mediated by B2 receptors in aortic coarctation (6 weeks)- and DOCA-salt (4 weeks)-induced hypertension. Before surgery, there was no difference between 129/SvEvTac and B2-KO mice in terms of blood pressure and heart weight, suggesting that kinins are not essential to maintaining normal blood pressure. DOCA-salt (volume expansion) or aortic coarctation (renin-dependent) induced similar hypertension and left ventricular hypertrophy (LVH) in 129/SvEvTac and B2-KO mice, suggesting that kinins do not play an essential role in the development of DOCA-salt- or aortic coarctation-induced hypertension. We found that B2 receptors mediate only the early (1 week) but not the late phase (4 weeks) of the chronic hypotensive effect of ACEi in DOCA-salt hypertension. On the other hand, chronic ACE inhibition prevented the development of hypertension and LVH in both 129/SvEvTac and B2-KO mice given DOCA-salt or subjected to aortic coarctation, suggesting that kinins do not participate in the chronic antihypertensive and antihypertrophic effects of ACEi in these 2 models of hypertension. Thus, in mice, kinins acting via B2 receptors do not participate in (1) maintenance of normal basal blood pressure, (2) establishment and maintenance of hypertension induced by DOCA-salt or aortic coarctation, and (3) chronic antihypertensive and cardiac antihypertrophic effects of ACEi in DOCA-salt and aortic coarctation hypertension.
 ...
PMID:Effect of ACE inhibitor on DOCA-salt- and aortic coarctation-induced hypertension in mice: do kinin B2 receptors play a role? 1060 Nov 37

The renin-angiotensin system is believed to play important roles in the development of acute myocardial infarction, and gene polymorphisms may also be involved. To investigate the genetic background in patients with acute myocardial infarction, we performed a case control study in a Japanese population. The study included 150 patients with acute myocardial infarction and 150 healthy, age- and sex-matched controls. We examined polymorphisms of angiotensin II type 1 receptor (1 166 A / C), type 2 receptor (3123 C / A), and bradykinin B2 receptor (-58 T / C) in these subjects. The allelic frequencies of angiotensin II type I receptor C and angiotensin II type 2 receptor A were significantly higher in the acute myocardial infarction subjects than in the control subjects, and this tendency was more significant in the younger patients. The combined ratios of angiotensin II type 1 receptor C and type 2 receptor A alleles in patients under 64 years old were significantly higher than in their older counterparts. However the total numbers of conventional coronary risk factors (hypertension, hypercholesterolemia, diabetes mellitus, and smoking) in individual subjects were not significantly different between younger and older patients. These polymorphisms were found to be involved in the development of acute myocardial infarction, particularly in the younger patients, and it was concluded that the incidence of acute myocardial infarction might be reduced by management from the genotypes.
 ...
PMID:Genetic background in patients with acute myocardial infarction. 1132 3

Acute systemic blockade of nitric oxide (NO) production by nonselective inhibitors of NO synthase (NOS) isoforms, including N(G)-nitro-L-arginine methyl ester (L-NAME) and N(G)-nitro-L-arginine (L-NNA), has been shown to produce a long-lasting pressor response in conscious and anaesthetised animals. The present study was undertaken to clarify whether the renin-angiotensin system contributes to the development of this pressor response to L-NNA. Systemic blood pressure and heart rate were continuously monitored in dogs anaesthetised with pentobarbital. Plasma renin activity in the blood obtained from a femoral artery and a renal vein was measured by use of radioimmunoassay. The acute pressor response produced by the intravenous administration of L-NNA was accompanied by reduced renin activity in both systemic and renal vascular beds. Captopril, an angiotensin converting enzyme inhibitor, counteracted the pressor response to L-NNA, whereas candesartan, an angiotensin AT1-receptor antagonist, had no apparent effect on it. The counteraction by captopril of the L-NNA-induced pressor response was likely to be attributable to enhancement by captopril of depressor responses to bradykinin, as HOE-140, a bradykinin B2 receptor antagonist, neutralised the effect of captopril. These results suggest that the pressor response acutely produced by the intravenous injection of a NOS inhibitor is not mediated by the renin-angiotensin system in anaesthetised dogs.
 ...
PMID:Non-contribution of renin-angiotensin system to pressor response to N(G)-nitro-L-arginine in dogs. 1190 8

This study was addressed to evaluate the temporospatial pattern of key components of the kallikreinkinin system in human uterus in luteal phase (n = 7), early pregnancy (isolated spontaneous abortions, n = 11; ectopic pregnancies, n = 9), idiopathic preterm deliveries (n = 5), and term gestations (n = 12). Tissue kallikrein mRNA and protein and the type 2 bradykinin receptor (B2R) protein were expressed in luminal and glandular epithelium and in endothelial cells of stromal and myometrial blood vessels, while tissue kallikrein mRNA and B2R, but not tissue kallikrein protein, were observed in decidual cells and in arteriolar and myometrial muscle. A greater signal intensity for tissue kallikrein mRNA and protein and of B2R protein was observed in the early pregnancy samples. The sites and variations of the tissue kallikrein mRNA and protein and of the B2R protein in the human uterus and in fallopian tubes during the luteal phase and in pregnancy coincide with those described for other vasoactive effectors such as nitric oxide, prostacyclins, growth factors, and renin. The uterine localization of the main enzyme and receptor of the tissue kallikrein-kinin system in key sites for embryo attachment, implantation, placentation, maintenance of placental blood flow, and parturition supports the notion that the kallikreinkinin system participates in these processes, probably through vasodilation, increased vasopermeability, enhanced matrix degradation, stimulation of cell proliferation, and myometrial contractility.
 ...
PMID:Tissue kallikrein and bradykinin B2 receptor in human uterus in luteal phase and in early and late gestation. 1195 65

Angiotensin converting enzyme (ACE) inhibition leads to increased levels of bradykinin, cyclooxygenase-2 (COX-2), and renin. Since bradykinin stimulates prostaglandin release, renin synthesis may be regulated through a kinin-COX-2 pathway. To test this hypothesis, we examined the impact of bradykinin B2 receptor (B2R) gene disruption in mice on kidney COX-2 and renin gene expression. Kidney COX-2 mRNA and protein levels were significantly lower in B2R-/- mice by 40-50%. On the other hand, renal COX-1 levels were similar in B2R-/- and +/+ mice. Renal renin protein was 61% lower in B2R-/- compared to B2R+/+ mice. This was accompanied by a significant reduction in renin mRNA levels in B2R-/- mice. Likewise, intrarenal angiotensin I levels were significantly lower in B2R-/- mice compared to B2R+/+ mice. In contrast, kidney angiotensin II levels were not different and averaged 261+/-16 and 266+/-15fmol/g in B2R+/+ and B2R-/- mice, respectively. Kidney angiotensinogen, AT1 receptor and ACE activity were not different between B2R+/+ and B2R-/- mice. The results of these studies demonstrate suppression of renal renin synthesis in mice lacking the bradykinin B2R and support the notion that B2R regulation of COX-2 participates in the steady-state control of renin gene expression.
 ...
PMID:The Bradykinin B2 receptor is required for full expression of renal COX-2 and renin. 1461 84


<< Previous 1 2 3 4 5 6 Next >>